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Workplace Material Safety Data Sheet Common/Trade name Synonyms Chemical name CI# Chemical formula Chemical family Material uses DSL# CAS# Code Molecular weight Apo-Tramadol HCl Tablets 50 mg Tramadol Hydrochloride Tablets Brand Name: Ultram Not applicable. Not applicable. Not available. Not on the DSCL list. Not applicable. 42617 Not applicable. Pharmaceutical industry: Dosage form Therapeutic category: analgesic. TRAMADOL25125 WHMIS Protective Clothing TDG Air/Road/Rail Section 1. Product Identification and Uses Manufacturer Apotex Inc. 50 Steinway Blvd Etobicoke, Ontario Canada M9W 6Y3 Tel. (416) 675-0338 Supplier TorPharm Etobicoke, Ontario M9W 6Y3 Canada Tel. (416) 675-0338 APOTEX INC. Emergency phone (416)-749-9300 ext. 5555 For general information call ext. 8483 (8 AM-4 PM) DIN Not available. Chemical structure Not applicable. Not regulated under WHMIS: Covered by Food & Drug Act. Canadian Classifications 1 0 2 NFPA 2 Apotex Haz. Class Not expected to be hazardous under normal handling conditions. Possible hypersensitization. Section 2. Hazards Identification Potential Acute Health Effects Potential Chronic Health Effects Not regulated under WHMIS: Covered by Food & Drug Act. Remark CLASS D-2B: Material causing other toxic effects (TOXIC). WHMIS Eye contact Skin contact Slight inhalation Flush with copious quantities of water. If irritation persists, obtain medical advice. Not expected to result in hazardous effects. Flush with copious amounts of water. Seek medical attention if irritation persist. Not expected to result in hazardous effects. Section 3. First Aid Measures Hazardous skin contact Continued on Next Page Page Number: 2 Apo-Tramadol HCl Tablets 50 mg Not expected to be hazardous. It is good practice to rinse mouth thoroughly with water and drink a cup of water to minimize discomfort. Hazardous inhalation Slight ingestion Hazardous ingestion Remove from exposure. Persons developing serious hypersensitivity reactions must receive immediate medical attention. If not breathing give artificial respiration (use protective mask with one-way valve). If breathing is difficult give oxygen. Never give anything by mouth if victim is rapidly losing consciousness, or is unconscious or convulsing. Rinse mouth thoroughly with water. If breathing has stopped, trained personnel should begin artificial respiration (use protective mask with one-way valve), or if the heart has stopped, cardiopulmonary resuscitation (CPR) immediately. Seek medical attention. Overdosage: Serious potential consequences of overdosage are respiratory depression and seizure. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. While naloxone will reverse some, but not all, symptoms caused by overdosage with Tramadol the risk of seizures is also increased with naloxone administration. In animals convulsions following the administration of toxic doses of tramadol could be suppressed with barbiturates or benzodiazepines but were increased with naloxone. Naloxone administration did not change the lethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period. Tramadol hydrochloride 73806-49-2 50 Tramadol: TDLo: 16 mg/kg/4D (intermittent-woman) LD50: 228 mg/kg (oral-rat) Toxicity values of the hazardous ingredients Section 4. Composition and Information on Ingredients Name CAS # % (w/w) TLV Not available. The product is: Autoignition temperature Fire degradation products Flash points Fire extinguishing procedures Flammable limits Flammability Not available. Combustible. These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...). Not available. Not available. Extinguisher media: water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials. Special fire fighting procedures: As with all fires, evacuate personnel to safe area. Firefighters should use self-contained breathing equipment and protective clothing. Not available No additional remark. Remark Risks of explosion Risks of explosion of the product in presence of mechanical impact: No. Risks of explosion of the product in presence of static discharge: Not available. Remark No additional remark. Section 5. Fire Fighting Measures Small spill and leak Large spill and leak Vacuum or sweep up spillage. Avoid dust. Place spillage in appropriate labeled solid pharmaceutical waste class 261A container for waste disposal. Wash contaminated clothing before reuse. Ventilate area and wash spill site. Follow appropriate Safe Work Practice. Use a shovel to put the material into a appropriate labeled waste disposal container. Finish cleaning by spreading water on the contaminated surface. Label and dispose as pharmaceutical waste class 261A. Follow appropriate Safe Work Practices. Section 6. Accidental Release Measures Protective Clothing Pictograms in case of large spill and/or high exposure levels Continued on Next Page Page Number: 3 Apo-Tramadol HCl Tablets 50 mg Protective clothing in case of large spill Covering uniform. Gloves. Storage Precautions Section 7. Handling and Storage In case of insufficient ventilation, wear suitable respiratory equipment. Avoid breathing dust. Wash thoroughly after handling. Dispose of as pharmaceutical waste Class 261A. Store at room temperature (15-30°C) , in a dry place, out of direct sunlight, in a tightly closed container. Engineering Controls Personal Protection Exposure to this material can be controlled in many ways. The measures appropriate for a particular worksite depend on how this material is used and on the extent of exposure. This general information can be used to help develop specific control measures. Ensure that control systems are properly designed and maintained. Comply with occupational, environmental, fire, and other applicable regulations. Engineering methods to control hazardous conditions are preferred. Methods include mechanical (local exhaust) ventilation, process or personnel enclosure and control of process conditions. Administrative controls and personal protective equipment may also be required. Supply sufficient replacement air to make up for air removed by exhaust system. Exposure Limits Section 8. Exposure Controls/Personal Protection Protective Clothing (Pictograms) Covering uniform. Gloves. Not available. PERSONAL PROTECTIVE EQUIPMENT : Under normal work conditions, the use of personal protective equipment is not expected to be required. However major spills should require the use of designated personal protective equipment. If engineering controls and work practices are not effective in controlling exposure to this material, then wear suitable personal protective equipment including approved respiratory protection. Have appropriate equipment available for use in emergencies such as spills or fire. If the physical state of the finished product is altered by crushing, grinding or breakage, appropriate PPE may be required including dust respirator. Refer to the CSA Standard Z94.4-M1982, "Selection, Care, and Use of Respirators," available from the Canadian Standards Association, Rexdale, Ontario, M9W 1R3. RESPIRATORY PROTECTION GUIDELINES : Under normal work conditions, the use of personal protective equipment is not expected to be required. However major spills should require the use of designated personal protective equipment. EYE/FACE PROTECTION : Not required under normal working conditions. SKIN PROTECTION : The use of gloves is required for Good Manufacturing Practices (GMP) compliance. RESISTANCE OF MATERIALS FOR PROTECTIVE CLOTHING : Guidelines : GOOD: Natural, butyl or styrene-butadiene rubber (SBR), neoprene, nitrile, polyvinyl chloride (PVC), polyurethane, nitrile+PVC, neoprene+SBR, neoprene+natural rubber, SBR/neoprene NOTE: Resistance of specific materials can vary from product to product. Evaluate resistance under conditions of use and maintain clothing carefully. EXPOSURE CONTROLS/PERSONAL PROTECTION COMMENTS : Remove contaminated clothing promptly. Launder before rewearing. Inform laundry personnel of contaminant's hazards. Do not eat, drink or smoke in work areas. Wash hands thoroughly after handling this material. Maintain good housekeeping. Section 9. Physical and Chemical Properties Physical state and appearance Volatility pH (1% soln/water) Odor Color Taste Odor threshold Solid. (Film-coated, capsule-shaped tablets) Not applicable. Not available. White. Not available. Not available. Not available. Continued on Next Page Page Number: 4 Apo-Tramadol HCl Tablets 50 mg Melting point/ Freezing point Boiling point Vapor pressure Specific gravity Vapor density Water/oil dist. coeff. Ionicity (surface active agent) Dispersion properties Solubility Not available. Not available. Not available. Not available. Not available. Not available. Not available. Soluble in water. Critical temperature Not available. Instability temperature Not available. Conditions of instability Not available. Evaporation rate See solubility. Not applicable. Hazardous decomp. products Stability Corrosivity Reactivity/ Incompatibility Remark Degradability Remark Normally stable. Not available. Not corrosive Not available. No additional remark. No additional remark. Not available. Section 10. Stability and Reactivity Toxicity data Remark Routes of entry Long-term effects As the product is a solid dosage form, the major route of entry is ingestion. Other routes of entry, including inhalation, skin and eye contact may occur only under certain circumstances. Tramadol: RTECS#: GV8925000 TDLo: 16 mg/kg/4D (intermittent-woman) LD50: 228 mg/kg (oral-rat) Target organ: Centaral nervous system Possible hypersensitization. Carcinogenicity: A slight, but statistically significant, increase in two common murine tumors, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice (dosing orally up to 30 mg/kg for approximately two years, although the study was not done with the Maximum Tolerated Dose). This finding is not believed to suggest risk in humans. No such finding occurred in a rat carcinogenicity study. Reproductive Toxicity: No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male rats and 75 mg/kg in female rats. Teratogenicity: There are no adequate and well-controlled studies in pregnant women. Tramadol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pragnancy category C. Tramadol has been shown to be embryotoxic and fetotoxic in mice, rats and rabbits at maternally toxic doses 3 to 15 times the maximum human dose or higher (120 mg/kg in mice, 25 mg/kg or higher in rats and 75 mg/kg or higher in rabbits), but was not teratogenic at these dose levels. No harm to the fetus due to tramadol was seen at The toxicological properties have not been thoroughly investigated. Section 11. Toxicological Information Continued on Next Page Page Number: 5 Apo-Tramadol HCl Tablets 50 mg Short-term effects and Signs & Symptoms of overexposure Remark Remark Possible eye, skin, gastrointestinal and/or respiratory tract irritation. Dosage: Tramadol should be started at 25 mg/day qAM and titrated in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg q.i.d.). Thereafter the total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, Tramadol 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day. The most frequently reported adverse reactions were in the central nervous system and gastrointestinal system. A variety of other adverse events were reported infrequently in patients taking tramadol during clinical trials: Coordination disturbance; Paresthesia; Cognitive dysfunction; Euphoria; Nervousness; Sleep disorder Hallucinations; Tremor; Amnesia; Difficulty in concentration; Abnormal gait Gastrointestinal Abdominal pain; Anorexia; Flatulence Musculoskeletal Hypertonia Respiratory Dyspnea Skin Rash Urticaria, Vesicles Special Senses Visual disturbance Dysgeusia Urogenital Urinary retention; Dysuria; Menstrual disorder Urinary frequency; Menopausal symptoms. A causal relationship between tramadol and these events has not been determined. However, the most significant events are listed below as alerting information to the physician: Body as a whole: Suicidal tendency. Cardiovascular: Abnormal ECG, hypertension, myocardial ischemia, palpitations. Central Nervous System: Migraine. Gastrointestinal: Gastrointestinal bleeding, hepatitis, stomatitis. Laboratory abnormalities: Creatinine increase, elevated liver enzymes, hemoglobin decrease, proteinuria. Sensory: Cataracts, deafness, tinnitus. Overdose: Cases of overdose with tramadol have been reported. Estimates of ingested dose in foreign fatalities have been in the range of 3 to 5 g. A 3 g intentional overdose by a patient in the clinical studies produced emesis and no sequelae. The lowest dose reported to be associated with fatality was possibly between 500 and 1000 mg in a 40 kg woman, but details of the case are not completely known. doses that were not maternally toxic. Mutagenicity: Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mutation tests in mice, chromosome aberration test in Chinese hamsters, and bone marrow micronucleus tests in mice and Chinese hamsters. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans. The above adverse effects are based on clinical studies. Medical conditions aggravated by exposure: Hypersensitivity to material, in cases of acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Section 12. Ecological Information Ecotoxicity Not available. BOD5 and COD5 Products of Biodegradation Toxicity of the Products of Biodegradation Special Remarks on the Products of Biodegradation Not available. Possibly hazardous short term degradation products are not likely. However, long term degradation products may arise. The products of degradation are less toxic than the product itself. No additional remark. Section 13. Disposal Considerations Waste Disposal Collect in sealed containers and place in appropriate labeled pharmaceutical solid waste class 261A container according to internal and external standards and procedures. Follow all appropriate safe work procedures and federal, provincial and local regulations for disposal. Use only licensed disposal and waste hauling companies. Section 14. Transport Information TDG, IATA, IMDG Not controlled under TDG (Canada). UN Not applicable (PIN and PG). Continued on Next Page Page Number: 6 Apo-Tramadol HCl Tablets 50 mg Special Provisions for Transport Not applicable. Section 15. Other Regulatory Information and Pictograms 0 1 2 This product is not classified according to the EU regulations. USA Classifications HCS (Hazardous Communication System) (OHSA, U.S.A.) DSCL Risk (R) and Safety (S) Phrases Hazardous Material Information System (U.S.A.) National Fire Protection Association (U.S.A.) Health Fire Hazard Reactivity Specific Hazard DOT (Department of Transportation) (U.S.A) (Pictograms) DSCL (Dangerous Substances Classifications) (Europe) (Pictograms) ADR (European Agreement of Dangerous goods by Road) (Pictograms) **NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD INDEX** NFPA-HEALTH-blue :2-Hazardous to health. NFPA-FLAMMABILITY-red :1-Materials that must be preheated before ignition can occur. NFPA-REACTIVITY-yellow :0-Normally stable. Not an HCS controlled material in USA. European Classifications Other Regulations Not available. Not controlled under ADR (Europe). Not a DOT controlled material (United States). Personal Protection Reactivity Fire Hazard Health Hazard 2 * - Chronic hazard indicator X - See Section 8 1 0 X Section 16. Other Information Validation date: (year.month) References The Merck Index, twelfth edition HSBD & RTECS Database RxList Monographs Physicians Desk Reference MSDS: Continued on Next Page Page Number: 7 Apo-Tramadol HCl Tablets 50 mg Validated on 11/04/2005. Printed 11/04/2005. Apotex Inc. 150 Signet Drive Weston (Toronto), Ontario Canada M9L 1T9 (416) 749-9300 Other Special Considerations SAMPLING AND ANALYSIS : Use appropriate instrumentation and sampling strategy (location, timing, duration, frequency, and number of samples). Interpretation of the sampling results is related to these variables and the analytical method. OSHA method IMISC136 has been published, but is not validated. Notice to Reader To the best of our knowledge, the information contained herein is accurate. However, neither the above named supplier nor any of its subsidiaries assumes any liability whatsoever for the accuracy or completeness of the information contained herein. Final determination of suitability of any material is the sole responsibility of the user. All materials may present unknown hazards and should be used with caution. Although certain hazards are described herein, we cannot guarantee that these are the only hazards that exist.